USF-1 as an Inhibitor of Mammary Gland Carcinogenesis

Abstract

Abstract : The hypothesis tested in this proposal is that overexpression of USF in the mammary glands of transgenic mice will inhibit myc-dependent tumorigenesis. To test this hypothesis, a transgene was constructed to target the overexpression of FLAG-tagged USF-2 to the mammary glands of virgin transgenic mice under the control of the mouse mammary tumor virus (MMTV) long terminal repeat. The transgene was evaluated in transfected cells in culture, and then injected into fertilized FVB mouse embryos. A total of 370 embryos were injected and transferred into recipient females resulting in 11 pregnancies. From these a total of 84 offspring were obtained, 12 of which were positive for the transgene. Females from the Fo and F1 generations of each line were screened for transgene expression by western blotting with an antibody specific for the FLAG peptide. Detectable expression was observed in a mammary gland from a single lactating Fo female. However, no expression was observed in any of the nonlactating virgin female F1 mice tested. In addition the single Fo female that was positive for transgene expression during lactation has thus far failed to produce viable offspring. This report discusses the implications of this data and suggests possible alternatives for testing the above hypothesis.